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PDBsum entry 1lp9
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Immune system PDB id
1lp9

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
275 a.a. *
100 a.a. *
194 a.a. *
237 a.a. *
Ligands
ALA-LEU-TRP-GLY-
PHE-PHE-PRO-VAL-
LEU ×2
Waters ×416
* Residue conservation analysis
PDB id:
1lp9
Name: Immune system
Title: Xenoreactive complex ahiii 12.2 tcr bound to p1049/hla-a2.1
Structure: Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a, h. Synonym: class i mhc, a2.1. Engineered: yes. Beta-2-microglobulin. Chain: b, i. Synonym: hdcma22p. Engineered: yes. Self-peptide p1049.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a 0201. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: this sequence occurs naturally in humans, but is
Biol. unit: Pentamer (from PQS)
Resolution:
2.00Å     R-factor:   0.221     R-free:   0.253
Authors: J.Buslepp,H.Wang,W.E.Biddison,E.Appella,E.J.Collins
Key ref:
J.Buslepp et al. (2003). A correlation between TCR Valpha docking on MHC and CD8 dependence: implications for T cell selection. Immunity, 19, 595-606. PubMed id: 14563323 DOI: 10.1016/S1074-7613(03)00269-3
Date:
07-May-02     Release date:   11-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens
Seq:
Struc: 		365 a.a.
275 a.a.*
Protein chains
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
100 a.a.*
Protein chains
Pfam   ArchSchema ?
P01849  (TCA_MOUSE) -  T-cell receptor alpha chain constant from Mus musculus
Seq:
Struc: 		136 a.a.
194 a.a.
Protein chains
Pfam   ArchSchema ?
P04213  (TVB5_MOUSE) -  T-cell receptor beta chain V region C5 (Fragment) from Mus musculus
Seq:
Struc: 		122 a.a.
237 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 27 residue positions (black crosses)

 

 
DOI no: 10.1016/S1074-7613(03)00269-3 Immunity 19:595-606 (2003)
PubMed id: 14563323  
 
 
A correlation between TCR Valpha docking on MHC and CD8 dependence: implications for T cell selection.
J.Buslepp, H.Wang, W.E.Biddison, E.Appella, E.J.Collins.
 
  ABSTRACT  
 
T cell receptors (TCR) adopt a similar orientation when binding with major histocompatibility complex (MHC) molecules, yet the biological mechanism that generates this similar TCR orientation remains obscure. We show here the cocrystallographic structure of a mouse TCR bound to a human MHC molecule not seen by the TCR during thymic development. The orientation of this xenoreactive murine TCR atop human MHC deviates from the typical orientation more than any previously determined TCR/MHC structure. This unique orientation is solely due to the placement of the TCR Valpha domain on the MHC. In light of new information provided by this structure, we have reanalyzed the existing TCR/MHC cocrystal structures and discovered unique features of TCR Valpha domain position on class I MHC that correlate with CD8 dependence. Finally, we propose that the orientation seen in TCR recognition of MHC is a consequence of selection during T cell development.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The Structure of AHIII 12.2 Bound to Xenogeneic p1049/A2The stereo view of AHIII 12.2 TCR is depicted as a ribbon (Carson, 1987) in magenta (α chain) and blue (β chain). The A2 heavy chain is silver, β[2]m is cyan, and the p1049 peptide is gold. 		Figure 2.
Figure 2. The Orientations of TCR Docked on Class I MHC Are Not Conserved to DiagonalThe orientation of AHIII 12.2 docking is most orthogonal when compared to other TCR/pMHC structures and Vα positions fall into two distinct groups. Class I MHC from TCR/pMHC cocrystal structures were superimposed onto p1049/A2 bound to AHIII 12.2. Molecular surfaces of the Vα and Vβ domains from those TCR are shown in addition to the variable domains of AHIII 12.2 (green) in order to compare the orientations of the TCR on the MHC. (A) 2C (red), (B) KB5-C20 (light blue), (C) A6 (dark blue), (D) B7 (gold), (E) BM3.3 (cyan), and (F) LC13 (magenta). (G) JM22 (yellow). (H) The positions of the center of mass of each TCR Vα and Vβ domain are given pseudo-atoms and the positions connected by a line to demonstrate the orientation that each TCR docks onto the MHC. The different TCR are colored as in (A)–(G). The p1049/A2 complex is shown as a molecular surface representation with the peptide colored yellow. (I) The orientation of Vα/Vβ pairs of TCR docking on class II MHC compared to AHIII 12.2. HA1.7 is shown in dark blue and D10 in light blue. AHIII 12.2 is shown in green. (A)–(I) were constructed with Grasp (Nicholls et al., 1991).
 
  The above figures are reprinted by permission from Cell Press: Immunity (2003, 19, 595-606) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21364947 J.M.Khan, and S.Ranganathan (2011).
Understanding TR Binding to pMHC Complexes: How Does a TR Scan Many pMHC Complexes yet Preferentially Bind to One.
  PLoS One, 6, e17194.  
19148199 K.C.Garcia, J.J.Adams, D.Feng, and L.K.Ely (2009).
The molecular basis of TCR germline bias for MHC is surprisingly simple.
  Nat Immunol, 10, 143-147.  
  19177349 P.Kumar, A.Vahedi-Faridi, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2009).
Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity.
  Protein Sci, 18, 37-49.
PDB code: 3bo8
18342005 D.I.Godfrey, J.Rossjohn, and J.McCluskey (2008).
The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
  Immunity, 28, 304-314.  
18465769 D.S.Riddle, P.J.Miller, B.G.Vincent, T.B.Kepler, R.Maile, J.A.Frelinger, and E.J.Collins (2008).
Rescue of cytotoxic function in the CD8alpha knockout mouse by removal of MHC class II.
  Eur J Immunol, 38, 1511-1521.  
18726714 E.J.Collins, and D.S.Riddle (2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
  Immunol Res, 41, 267-294.  
18800968 K.M.Armstrong, K.H.Piepenbrink, and B.M.Baker (2008).
Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes.
  Biochem J, 415, 183-196.  
18456484 P.Marrack, K.Rubtsova, J.Scott-Browne, and J.W.Kappler (2008).
T cell receptor specificity for major histocompatibility complex proteins.
  Curr Opin Immunol, 20, 203-207.  
18308592 S.Dai, E.S.Huseby, K.Rubtsova, J.Scott-Browne, F.Crawford, W.A.Macdonald, P.Marrack, and J.W.Kappler (2008).
Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules.
  Immunity, 28, 324-334.
PDB codes: 3c5z 3c60 3c6l
18201888 S.Minguet, and W.W.Schamel (2008).
A permissive geometry model for TCR-CD3 activation.
  Trends Biochem Sci, 33, 51-57.  
17506031 A.M.McNicol, G.Bendle, A.Holler, T.Matjeka, E.Dalton, L.Rettig, R.Zamoyska, W.Uckert, S.A.Xue, and H.J.Stauss (2007).
CD8alpha/alpha homodimers fail to function as co-receptor for a CD8-dependent TCR.
  Eur J Immunol, 37, 1634-1641.  
17540778 B.Laugel, H.A.van den Berg, E.Gostick, D.K.Cole, L.Wooldridge, J.Boulter, A.Milicic, D.A.Price, and A.K.Sewell (2007).
Different T cell receptor affinity thresholds and CD8 coreceptor dependence govern cytotoxic T lymphocyte activation and tetramer binding properties.
  J Biol Chem, 282, 23799-23810.  
17694060 D.Feng, C.J.Bond, L.K.Ely, J.Maynard, and K.C.Garcia (2007).
Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.
  Nat Immunol, 8, 975-983.
PDB codes: 2pxy 2z31 2z35
17418792 L.A.Colf, A.J.Bankovich, N.A.Hanick, N.A.Bowerman, L.L.Jones, D.M.Kranz, and K.C.Garcia (2007).
How a single T cell receptor recognizes both self and foreign MHC.
  Cell, 129, 135-146.
PDB codes: 2e7l 2oi9
18007679 N.J.Felix, and P.M.Allen (2007).
Specificity of T-cell alloreactivity.
  Nat Rev Immunol, 7, 942-953.  
17825839 P.J.Miller, Y.Pazy, B.Conti, D.Riddle, E.Appella, and E.J.Collins (2007).
Single MHC mutation eliminates enthalpy associated with T cell receptor binding.
  J Mol Biol, 373, 315-327.
PDB codes: 2j8u 2jcc 2uwe
17459926 R.M.Brennan, J.J.Miles, S.L.Silins, M.J.Bell, J.M.Burrows, and S.R.Burrows (2007).
Predictable alphabeta T-cell receptor selection toward an HLA-B*3501-restricted human cytomegalovirus epitope.
  J Virol, 81, 7269-7273.  
17188005 S.Minguet, M.Swamy, B.Alarcón, I.F.Luescher, and W.W.Schamel (2007).
Full activation of the T cell receptor requires both clustering and conformational changes at CD3.
  Immunity, 26, 43-54.  
17011774 C.S.Clements, M.A.Dunstone, W.A.Macdonald, J.McCluskey, and J.Rossjohn (2006).
Specificity on a knife-edge: the alphabeta T cell receptor.
  Curr Opin Struct Biol, 16, 787-795.  
16840780 H.C.Chang, K.Tan, and Y.M.Hsu (2006).
CD8alphabeta has two distinct binding modes of interaction with peptide-major histocompatibility complex class I.
  J Biol Chem, 281, 28090-28096.  
16617112 L.K.Ely, T.Beddoe, C.S.Clements, J.M.Matthews, A.W.Purcell, L.Kjer-Nielsen, J.McCluskey, and J.Rossjohn (2006).
Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction.
  Proc Natl Acad Sci U S A, 103, 6641-6646.  
16551255 M.G.Rudolph, R.L.Stanfield, and I.A.Wilson (2006).
How TCRs bind MHCs, peptides, and coreceptors.
  Annu Rev Immunol, 24, 419-466.  
16872849 P.P.Yachi, J.Ampudia, T.Zal, and N.R.Gascoigne (2006).
Altered peptide ligands induce delayed CD8-T cell receptor interaction--a role for CD8 in distinguishing antigen quality.
  Immunity, 25, 203-211.  
16897816 S.Liang, W.Zhang, and A.Horuzsko (2006).
Human ILT2 receptor associates with murine MHC class I molecules in vivo and impairs T cell function.
  Eur J Immunol, 36, 2457-2471.  
15895191 B.Peters, J.Sidney, P.Bourne, H.H.Bui, S.Buus, G.Doh, W.Fleri, M.Kronenberg, R.Kubo, O.Lund, D.Nemazee, J.V.Ponomarenko, M.Sathiamurthy, S.P.Schoenberger, S.Stewart, P.Surko, S.Way, S.Wilson, and A.Sette (2005).
The design and implementation of the immune epitope database and analysis resource.
  Immunogenetics, 57, 326-336.  
16260763 H.Li, S.Van Vranken, Y.Zhao, Z.Li, Y.Guo, L.Eisele, and Y.Li (2005).
Crystal structures of T cell receptor (beta) chains related to rheumatoid arthritis.
  Protein Sci, 14, 3025-3038.
PDB codes: 2axh 2axj
15593303 J.C.Huang, R.J.Ober, and E.S.Ward (2005).
The central residues of a T cell receptor sequence motif are key determinants of autoantigen recognition in murine experimental autoimmune encephalomyelitis.
  Eur J Immunol, 35, 299-304.  
15664164 J.Kuball, F.W.Schmitz, R.H.Voss, E.A.Ferreira, R.Engel, P.Guillaume, S.Strand, P.Romero, C.Huber, L.A.Sherman, and M.Theobald (2005).
Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR.
  Immunity, 22, 117-129.  
15837811 J.L.Chen, G.Stewart-Jones, G.Bossi, N.M.Lissin, L.Wooldridge, E.M.Choi, G.Held, P.R.Dunbar, R.M.Esnouf, M.Sami, J.M.Boulter, P.Rizkallah, C.Renner, A.Sewell, P.A.van der Merwe, B.K.Jakobsen, G.Griffiths, E.Y.Jones, and V.Cerundolo (2005).
Structural and kinetic basis for heightened immunogenicity of T cell vaccines.
  J Exp Med, 201, 1243-1255.
PDB codes: 2bnq 2bnr 2bnu
15664161 J.Maynard, K.Petersson, D.H.Wilson, E.J.Adams, S.E.Blondelle, M.J.Boulanger, D.B.Wilson, and K.C.Garcia (2005).
Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity.
  Immunity, 22, 81-92.
PDB code: 1u3h
16096054 K.C.Garcia, and E.J.Adams (2005).
How the T cell receptor sees antigen--a structural view.
  Cell, 122, 333-336.  
15805102 M.Cebecauer, P.Guillaume, S.Mark, O.Michielin, N.Boucheron, M.Bezard, B.H.Meyer, J.M.Segura, H.Vogel, and I.F.Luescher (2005).
CD8+ cytotoxic T lymphocyte activation by soluble major histocompatibility complex-peptide dimers.
  J Biol Chem, 280, 23820-23828.  
15537658 M.Hülsmeyer, P.Chames, R.C.Hillig, R.L.Stanfield, G.Held, P.G.Coulie, C.Alings, G.Wille, W.Saenger, B.Uchanska-Ziegler, H.R.Hoogenboom, and A.Ziegler (2005).
A major histocompatibility complex-peptide-restricted antibody and t cell receptor molecules recognize their target by distinct binding modes: crystal structure of human leukocyte antigen (HLA)-A1-MAGE-A1 in complex with FAB-HYB3.
  J Biol Chem, 280, 2972-2980.
PDB code: 1w72
15802267 S.Huang, S.Gilfillan, M.Cella, M.J.Miley, O.Lantz, L.Lybarger, D.H.Fremont, and T.H.Hansen (2005).
Evidence for MR1 antigen presentation to mucosal-associated invariant T cells.
  J Biol Chem, 280, 21183-21193.  
15845547 T.Sandalova, J.Michaëlsson, R.A.Harris, J.Odeberg, G.Schneider, K.Kärre, and A.Achour (2005).
A structural basis for CD8+ T cell-dependent recognition of non-homologous peptide ligands: implications for molecular mimicry in autoreactivity.
  J Biol Chem, 280, 27069-27075.
PDB code: 1zhb
15489186 A.B.Sigalov (2004).
Multichain immune recognition receptor signaling: different players, same game?
  Trends Immunol, 25, 583-589.  
15040585 J.Nikolich-Zugich, M.K.Slifka, and I.Messaoudi (2004).
The many important facets of T-cell repertoire diversity.
  Nat Rev Immunol, 4, 123-132.  
14734119 N.R.Gascoigne, and T.Zal (2004).
Molecular interactions at the T cell-antigen-presenting cell interface.
  Curr Opin Immunol, 16, 114-119.  
15131131 T.K.Baxter, S.J.Gagnon, R.L.Davis-Harrison, J.C.Beck, A.K.Binz, R.V.Turner, W.E.Biddison, and B.M.Baker (2004).
Strategic mutations in the class I major histocompatibility complex HLA-A2 independently affect both peptide binding and T cell receptor recognition.
  J Biol Chem, 279, 29175-29184.  
14563309 B.Malissen (2003).
Glimpses at TCR trans-species crossreactivity.
  Immunity, 19, 463-464.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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